Significant benefits can be realized from electrochemically measuring analytes in fluidic samples (i.e., biological or environmental). For example, individuals with diabetes can benefit from measuring glucose. Those potentially at-risk for heart disease can benefit from measuring cholesterols and triglycerides among other analytes. These are but a few examples of the benefits of measuring analytes in biological samples. Advancements in the medical sciences are identifying a growing number of analytes that can be electrochemically analyzed in a fluidic sample.
The accuracy of present approaches to electrochemically measuring analytes such as glucose can be negatively affected by a number of confounding variables including variations in reagent thickness, wetting of the reagent, rate of sample diffusion, hematocrit (Hct), temperature, salt and other confounding variables. These confounding variables can cause an increase or decrease in an observed magnitude of, for example, a current response that is proportional to glucose, thereby causing a deviation from the “true” glucose concentration.
A number of approaches are known for correcting errors attributable to variation in test sample and biosensor characteristics. Some approaches seek to perform active correction on analyte measurements. For example, US Patent Application Publication No. 2009/0236237 discloses biosensor measurement systems including temperature correction algorithms for correcting analyte measurements based upon measurements of the ambient temperature, the temperature of the biosensor itself, or the time between when a biosensor is attached to a measurement device and a sample is provided to the biosensor. In another example, U.S. Pat. No. 7,407,811 discloses a system and method for measuring blood glucose that corrects for variation in temperature, Hct and other confounding variables by measuring impedance of a blood sample to an AC excitation and using the impedance (or impedance derived admittance and phase information) to correct for the effects of such interferents.
Other approaches seek to control the physical characteristics of biosensors. For example, U.S. Pat. No. 7,749,437 discloses methods for controlling reagent thickness and uniformity.
There also have been attempts to perform electrochemical analyte measurements using pulsed signals. For example, Barker et al. disclose that an alternating polarographic square wave potential can be applied to a test cell and that the amplitude of the AC current response was measured just before each change of applied voltage to detect concentrations of metallic ions. See, Barker et al. (1952) Int'l Congr. Anal. Chem. 77:685-696. Barker et al. also disclose that their method ameliorates the undesirable effect of the rate of double-layer capacitance current on the sensitivity of an A/C polarograph.
In addition, Gunasingham et al. disclose a pulsed amperometric detection method for a mediator-based enzyme electrode that applies a potential pulse signal to a working electrode and measures a current response. See, Gunasingham et al. (1990) J. Electroanal. Chem. 287:349-362. The pulse signal alternates between a base potential and an excitation potential. Excitation potential pulse durations ranging from less than 100 msec to more than 1 sec are disclosed, and current sampling occurred during the last 16.7 msec of each oxidation potential pulse. See also, U.S. Pat. No. 5,312,590, which discloses applying a pulsed excitation sequence that is alternated between 0 V for 300-500 msec and 150 mV for 50-60 msec.
Furthermore, Champagne et al. disclose a voltammetric measurement method that applies variable potential signals to electrodes of an electrochemical cell to produce an electrochemical reaction and measures the resulting current response. See, U.S. Pat. No. 5,980,708. A square waveform potential was used to drive test cell electrodes. Positive and negative current responses were integrated over time periods within a current response, and the integrated currents were summed to calculate a current measurement. An example of a pulsed voltammetric measurement method disclosed therein used an input signal having a pulse height of 30 mV, a step height of 5 mV, a cycle period of 100 msec, a pulse width of 40 msec and a sample time of 35 msec. Champagne et al. further disclose ensuring that the rise time of a square wave signal applied to an electrode is sufficiently rapid to permit current measurement.
Wu et al. discloses using gated amperometric pulse sequences including multiple duty cycles of sequential excitation potentials and recoveries. See, US Patent Application Publication No. 2008/0173552. The excitation potentials provide a constant voltage to an electrochemical cell. A current response was generated during excitation potentials and measured. The current was reduced during recovery by at least half and preferably to zero. The reduced recovery current was provided by an open circuit condition to the electrochemical cell. Wu et al. thus disclose that preferred recoveries are fundamentally different from applying a zero potential recovery since these recoveries provide an independent diffusion and analyte reaction during the recovery without the effects of an applied electric potential even of zero volts.
A similar gated amperometric measurement method is disclosed by Wu, during which a recovery the electrical signal is in an off state that includes time periods when an electrical signal is not present but does not include time periods when an electrical signal is present but essentially has no amplitude. See, US Patent Application Publication No. 2009/0145779. The off state was provided by opening an electrical circuit mechanically, electrically, or by other methods. Moreover, US Patent Application Publication No. 2008/0179197 by Wu discloses gated voltammetric pulse sequences including multiple duty cycles of sequential excitations and recoveries. The excitations provided a linear, cyclic or acyclic excitation to an electrochemical cell during which response currents were measured while a applied potential was varied linearly with time. The recoveries also were provided in an open circuit condition to the electrochemical cell.
Current methods and systems therefore provide some advantages with respect to convenience; however, there remains a need for new methods of electrochemically measuring an analyte in a fluid sample even in the presence of confounding variables.